Alkyl 4-Alkoxyvalerates: Characterization and Application in Pd-Catalyzed Aminocarbonylation of Iodo(hetero)arene Compounds.

Abstract

The palladium-catalyzed aminocarbonylation is one of the most effective methods for the synthesis of carboxamides having great importance. Replacing fossil-based organic solvents in this routinely used catalytic protocol with biomass-derived media is crucial for developing environmentally safe alternatives and towards sustainability considerations. In this study, the open-chain derivatives of bio-originated substance γ-valerolactone i. e. alkyl 4-alkoxyvalerates (alkyl: methyl, ethyl, and propyl) were characterized and tested as potential polar aprotic alternatives of fossil-based common N,N-dimethylformamide (DMF) in aminocarbonylation protocols. First, the temperature-dependent physicochemical properties of alkyl 4-alkoxyvalerates were determined. Based on their characteristics, methyl 4-methoxyvalerate (Me-4MeOV) was selected and introduced in the Pd-catalyzed aminocarbonylation of iodobenzene and morpholine as a model reaction, and an optimization study was carried out. Using the optimized conditions, several substituted iodobenzenes, as well as heteroaryl iodides, were successfully applied resulting in the target carboxamides selectively in short reaction time. Furthermore, the aminocarbonylation of iodobenzene in the presence of various amines was also accomplished extending the scope of the carboxamides produced in this alternative medium. Considering our observations, such as high conversions (up to 95 %) in short reaction time and selective amide formation, it has been justified that Me-4MeOV could be an appropriate alternative medium in aminocarbonylation protocols.